EP0813841A2 - Chirurgische Nähnadel sowie deren Herstellungsverfahren - Google Patents

Chirurgische Nähnadel sowie deren Herstellungsverfahren Download PDF

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Publication number
EP0813841A2
EP0813841A2 EP97116567A EP97116567A EP0813841A2 EP 0813841 A2 EP0813841 A2 EP 0813841A2 EP 97116567 A EP97116567 A EP 97116567A EP 97116567 A EP97116567 A EP 97116567A EP 0813841 A2 EP0813841 A2 EP 0813841A2
Authority
EP
European Patent Office
Prior art keywords
needle
head
surgical suturing
surgical
shaft
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP97116567A
Other languages
English (en)
French (fr)
Other versions
EP0813841B1 (de
EP0813841A3 (de
Inventor
Jannaih S. Prasad
Robert Maurer
Paul Kapralos
John E. Buzerak
Charles L. Putnam
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Covidien AG
Original Assignee
American Cyanamid Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by American Cyanamid Co filed Critical American Cyanamid Co
Publication of EP0813841A2 publication Critical patent/EP0813841A2/de
Publication of EP0813841A3 publication Critical patent/EP0813841A3/de
Application granted granted Critical
Publication of EP0813841B1 publication Critical patent/EP0813841B1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/04—Surgical instruments, devices or methods, e.g. tourniquets for suturing wounds; Holders or packages for needles or suture materials
    • A61B17/06—Needles ; Sutures; Needle-suture combinations; Holders or packages for needles or suture materials
    • A61B17/06066—Needles, e.g. needle tip configurations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/04—Surgical instruments, devices or methods, e.g. tourniquets for suturing wounds; Holders or packages for needles or suture materials
    • A61B17/06—Needles ; Sutures; Needle-suture combinations; Holders or packages for needles or suture materials
    • A61B17/06004—Means for attaching suture to needle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00853—Material properties low friction, hydrophobic and corrosion-resistant fluorocarbon resin coating (ptf, ptfe, polytetrafluoroethylene)

Definitions

  • the present invention relates to a design and method of manufacturing a surgical suturing needle that can be used generally for adjoining or closing adjacent portions of skin or tissue. More particularly, the suturing needle design and manufacturing process of the present invention are directed to a new class of suturing needle particularly suitable in plastic and reconstructive suturing applications.
  • Suturing needles for applying sutures, or stitches, by hand in cutaneous and subcutaneous tissues are well known in the art.
  • the sutures are typically used to close wounds or adjoin adjacent tissue, often at the conclusion of a surgical procedure.
  • Conventional suturing needles are usually made from a cut blank of material such as stainless steel.
  • the cut blank is metal-worked using well known machining techniques to form a surgical suturing needle.
  • the needle generally includes a shaft, a rear end portion with means to grip or secure a suturing thread and a needle head at a front end portion for puncturing skin and tissue through which the needle travels.
  • the needle head typically includes a sharpened needle tip at its distal end and cutting edges.
  • Needle sharpness is an important consideration in designing and manufacturing surgical suturing needles.
  • Needle sharpness is typically defined in terms of a so-called penetration force -- the force necessary for a needle point to puncture, or penetrate, the tissue.
  • the penetration force is primarily determined by the design and sharpness of the needle point.
  • needle sharpness is also affected by a drag force of the needle as it travels through the tissue. The ability of the needle to pass smoothly through the tissue is a desirable characteristic.
  • the drag force of the needle depends upon the design and sharpness of the needle, especially the needle head.
  • the quality of a lubricating coating on the needle also affects the drag force. For example, if the lubricating coating on the needle wears off, the drag force on the needle increases with each pass of the needle through the tissue. This effect could give the surgeon-user the false impression that the needle is failing to retain its sharpness.
  • the strength of a suturing needle is a measure of its ability to resist bending and is determined by such factors as (a) the material selected to make the needle, (b) the cross-sectional shape of the needle, and (c) the heat treatment process received by the needle during manufacturing.
  • needle strength should be balanced by needle ductility, which is defined in terms of the ability of the needle to be reshaped after it flexes from its original shape.
  • a surgical needle with good strength characteristics but having little or no ductility can be brittle and may snap and break during use. In use, the surgical needle is held at its rear end by a needle holder and the needle tip is forced against the tissue to be sutured.
  • the needle holder is typically used to grip and stabilize the needle as it passes through the tissue.
  • the subject invention provides significant advances over conventional surgical suturing needles by improving needle attributes such as needle sharpness and resistance to bending or breaking during use as well as other desirable attributes.
  • surgical suturing needle that comprises a needle shaft having a rectangular cross-section, and a multi-sided needle head having a needle point with a plurality of cutting edges extending axially from the needle head and defining sides of the needle head.
  • a transitional portion adjoins the needle shaft and the needle head and has a maximum width greater than the width of the needle shaft. This design may be called “cobra-headed.”
  • the method of manufacturing a surgical suturing needle in accordance with a preferred embodiment of the present invention comprises the step of metal-working a needle blank to form a shaft portion, having a rectangular cross-section, that terminates in a needle point and having a plurality of cutting edges.
  • the needle head is then worked to form a transition portion between the shaft portion and the needle head that has a width greater than the width of the shaft portion.
  • the cutting edges extend axially from the needle point at least to this transition portion. Finally the needle point and cutting edges are sharpened.
  • the surgical suturing needle of the present invention is designed and manufactured to possess attributes of primary importance in suturing needles.
  • the suturing needle of the present invention is designed with superior needle sharpness to penetrate and travel easily through the cutaneous and subcutaneous layers of tissue.
  • the surgical needle of the subject invention also has superior strength and resistance to bending and/or breaking during use.
  • a three-fold approach is used to produce the surgical suturing needle of the subject invention.
  • each component of this three-fold approach is interdependent, and is preferably used in conjunction with the other components to achieve an optimum suturing needle.
  • the first component is proper selection of the material for the surgical needle to obtain superior physical characteristics.
  • the needle is designed in a way to enhance its penetration characteristic and the ability to travel through the tissue and to provide it with superior physical characteristics, and third, particular manufacturing steps are used in metal-working the needle to achieve optimum benefits of the needle design.
  • the choice of materials is of primary importance to the physical characteristics, that is, strength, ductility and resistance to bending or breaking of the needle.
  • the cross-sectional shape and dimensions of the needle and the heat-treating process which the needle receives during the manufacturing process also contribute to the physical characteristics of the needle.
  • the suturing needle of the present invention is preferably made from AISI 302 type stainless steel.
  • AISI types 301 or 304 which possess similar characteristics to AISI 302, can also be used.
  • These '300' series stainless steels which typically have a tensile strength of 228702940-246295470 kg/cm 2 (325,000-350,000 lbs/in 2 ), attain their high strength from undergoing cold working as the material is converted from an ingot to wire of the desired diameter.
  • the design of the surgical needle of the present invention contributes to both its strength and resistance to bending and to its ability to easily pierce and travel through the tissue to be sutured.
  • the finished needle 10 is shown in Figure 1A to have a curved needle shaft 12 with a needle head 14 at its distal end and a rear end portion 16 at its proximal end.
  • the needle head 14 terminates in a needle point 18 for piercing the skin or tissue.
  • the rear end portion 16 includes an axial hole 20 for receiving and securing a suturing thread.
  • other means for securing the suturing thread within the proximal end of the needle shaft such as for example, a crimping channel, are also contemplated.
  • the cross-sectional area of the needle shaft 12 is rectangular in shape as shown in Figure 1B. While conventional needles typically have cross-sections that are round or triangular, the rectangular cross-section of the present invention provides strength superior to that of conventional cross-sections over the same area.
  • the major axis A-A of the rectangular cross-section is in the plane of curvature, i.e, the X-Y plane, of the needle and the minor axis B-B lies in the X-Z plane (as seen in Figures 1A and 2A).
  • an excessively pronounced rectangular shape can further increase the strength of the needle, such a cross-sectional shape reduces the stability of the needle in a needle holder. Therefore, it is preferable to shape the rectangular cross-section to have a major axis to minor axis ratio of 1.2 or less.
  • the needle head 14 is shaped to have three sides 22 tapering toward the distal end of the needle to form the needle point 18.
  • the cross-section of the needle point is triangular in shape as shown in Figures 1C and 2C, and the three corners of the triangle, that is, the edges adjoining each adjacent side 22, form cutting edges 24 for slicing the cutaneous and subcutaneous tissue.
  • the included angle A of the needle point is preferably between 25° and 29° as shown in Figure 3. A smaller included angle would reduce the necessary penetration force but would also increase the susceptibility of the needle point to damage during fabrication or use. On the other hand, a larger included angle increases the durability of the needle point but also requires an undesirable increase in force necessary to penetrate the cutaneous tissue.
  • the needle head 14 of the subject invention also features a cobra head shape, wherein the widest portion of the needle head has a width W 2 slightly greater than the width W 1 of the needle shaft as shown in Figure 3.
  • the widest portion of the needle head 14 is identified as transition portion 21 in Figures 3, 4 and 7.
  • the cutting edges 24 extend from the needle point 18 to at least the widest part of the needle head 14. In this manner, the three cutting edges 24 slice the tissue as the needle head passes therethrough and provide an opening slightly larger than the shaft 12 of the needle, thus significantly reducing the drag force, and allowing the shaft to pass easily through the tissue.
  • the length of the cutting edges are preferably between 3 and 7 times the diameter of the wire, or cut blank, used for the needle.
  • the manufacturing process of the subject invention begins with selection of a cut blank from a coil of wire made of one of the preferred materials discussed above.
  • the cut blank 26 is shown in Figure 5A, and has a conventional round cross-section 27 as shown in Figure 5B.
  • the cut blank is worked with a conventional press or swaging machine to form the needle shaft 12 with a rectangular cross-section 13 as shown in Figures 6A and 6B.
  • the proximal end 16 of the needle shaft can retain its circular cross-section, and is machined to provide an axial hole 16, or other comparable means, for securing the suturing thread to the needle.
  • the three-sided needle head 14 is formed at the distal end by using, for example, a three-jaw toggle press or a swaging machine.
  • the three sides 22 are first worked to form a blunt end "cobra-head" type shape with transition portion 21 having a maximum width W 2 slightly larger than the width W 1 of the needle shaft 12 as described above.
  • the cutting edges 24 will also necessarily be curved as shown in Figure 6A, as the three-sided needle head 14 meets with the four-sided needle shaft 12. A coined preform of the suturing needle is thus formed at the manufacturing stage shown in Figures 6A and 7.
  • Progressively finer grinding media such as an abrasive belt, are then used to finish shaping the cobra head and form a needle point 18 at the distal end of the needle head.
  • the needle point and cutting edges are further honed to form sharp cutting edges.
  • the use of progressively finer sharpening media minimizes any burr formation on the cutting edges of the needle head.
  • the surgical needle is then curved to its appropriate shape at this stage of the manufacturing process by conventional means, making sure the major axis of the rectangular cross-section is in the plane of curvature of the needle as described above with reference to Figures 1A, 1B, 2A, and 2B.
  • the particular radius of curvature of the needle is a matter of design application and user preference.
  • a straight needle design can be used without departing from the scope of the invention.
  • the surgical needle is then exposed to an electrical field while being immersed in an acid bath.
  • This electrochemically prcessing step removes any burrs left from the grinding process and smooths without dulling the cutting edges of the needle head. While the actual amount of material removed in this step is very small, electrohoning can reduce by 30% to 40% the force necessary to penetrate the tissue. The time of exposure, temperature of the acid bath and the current density of the electrical field should be carefully controlled to obtain the maximum benefit of this step.
  • the temperature of the acid bath is preferably within a range of 54,4°C to 82,2°C (130° to 180°F), and more preferably around 66°C (150°F)
  • the time of exposure can range from 3 to 20 minutes, with 81 ⁇ 2 minutes found to be the optimum exposure time, and the preferred current density is 430.56 amps/m 2 (40 amps/ft 2 ), although a broader range of between 107.64 and 861,11 amps/m 2 (10 and 80 amps/ft 2 ) can be used depending upon the temperature of the acid bath and the time of exposure.
  • the metal-worked, fully shaped needle is then heat treated to increase its strength and resistance to bending.
  • the needles are exposed to a temperature of 371.1°C to 593.3°C (700° to 1100°F), and preferably between 427,67°C and 482,22°C (800° and 900°F), for a time period of between 1 to 4 hours.
  • the heat treated needles can then be coated with a lubricant to enhance passage of the needle through the tissue.
  • Conventional solutions for this purpose include silicones and Teflon.
  • the surgical suturing needle design of the subject invention is preferably made by the disclosed needle manufacturing process.
  • the benefits of the needle design of the subject invention can be realized even if the needle is made by conventional manufacturing techniques.
  • FIG 8 shows a table illustrating the comparative results of four groups of different sized needles.
  • Each group contains a suturing needle made in accordance with the subject invention, identified by source as "D + G", and two conventional models.
  • the first conventional needle in each group is marketed by Sulze and is shaped to have a three-sided needle head design and a body shape with a triangular cross-section.
  • the second conventional needle in each group is marketed by Ethicon and has a three-sided needle head design and a round body shape with flattened top and bottom portions. Some of the Ethicon needles also have a 'cobra-head' type head design.
  • the first measurement of needle performance is lowest in each group for the needles made in accordance with the subject invention.
  • the penetration force was measured using an average of 10 needles per lot, with three penetrations per needle through rabbit skin. As will be appreciated, lower penetration force is desirable, as this indicates superior needle sharpness and reduces tissue trauma.
  • the second measurement of needle performance is strength as measured in a moment force needed to bend the needle. This test was performed using a Tinius-Olsen Tester with an average of 10 needles per lot. As the table in Figure 8 illustrates, the 'D + G' needles required a greater moment force to bend the needles.
  • ductility was measured in the number of times a needle could be manually bent through 30° on either side of a nominal position without breaking. Again, an average of 10 needles per lot were tested.
  • the needles of the subject invention demonstrated superior ductility over conventional needles by withstanding a greater number of bends before breaking.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Surgical Instruments (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP97116567A 1993-04-30 1994-03-30 Verfahren zur Herstellung einer chirurgischen Nähnadel Expired - Lifetime EP0813841B1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/055,165 US5330441A (en) 1993-04-30 1993-04-30 Surgical suturing needle and method for making same
EP94105014A EP0633000B1 (de) 1993-04-30 1994-03-30 Chirurgische Nähnadel
US55165 2002-01-21

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
EP94105014.8 Division 1994-03-30
EP94105014A Division EP0633000B1 (de) 1993-04-30 1994-03-30 Chirurgische Nähnadel

Publications (3)

Publication Number Publication Date
EP0813841A2 true EP0813841A2 (de) 1997-12-29
EP0813841A3 EP0813841A3 (de) 1998-01-07
EP0813841B1 EP0813841B1 (de) 2001-02-28

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ID=21996062

Family Applications (2)

Application Number Title Priority Date Filing Date
EP97116567A Expired - Lifetime EP0813841B1 (de) 1993-04-30 1994-03-30 Verfahren zur Herstellung einer chirurgischen Nähnadel
EP94105014A Expired - Lifetime EP0633000B1 (de) 1993-04-30 1994-03-30 Chirurgische Nähnadel

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP94105014A Expired - Lifetime EP0633000B1 (de) 1993-04-30 1994-03-30 Chirurgische Nähnadel

Country Status (12)

Country Link
US (1) US5330441A (de)
EP (2) EP0813841B1 (de)
JP (2) JPH07400A (de)
KR (1) KR940023444A (de)
AT (2) ATE165963T1 (de)
AU (2) AU677822B2 (de)
CA (1) CA2122418C (de)
DE (2) DE69426785T2 (de)
DK (1) DK0633000T3 (de)
ES (1) ES2156325T3 (de)
TW (1) TW278028B (de)
ZA (1) ZA942974B (de)

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US5693454A (en) * 1996-01-24 1997-12-02 United States Surgical Corporation Two-sided photoetching process for needle fabrication
US5762811A (en) * 1996-01-24 1998-06-09 United States Surgical Corporation One-sided photoetching process for needle fabrication
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US5897572A (en) * 1996-10-11 1999-04-27 Cornell Research Foundation, Inc. Microsurgical suture needle
US5783001A (en) * 1996-11-14 1998-07-21 Ethicon, Inc. Process for the heat treatment of surgical needles by aging
US5814166A (en) * 1996-11-14 1998-09-29 Ethicon, Inc. Process for heat treating and tempering surgical needles
US5730732A (en) * 1996-12-04 1998-03-24 Ethicon, Inc. Non-magnetic stainless steel surgical needle
EP0975265B1 (de) * 1996-12-23 2003-06-25 Sherwood Services AG Gekrümmte chirurgische nadel und ihr herstellungsverfahren
US5928268A (en) * 1997-12-18 1999-07-27 Tyco Group S.A.R.L. Curved surgical needles and method of making the same
US6187000B1 (en) * 1998-08-20 2001-02-13 Endius Incorporated Cannula for receiving surgical instruments
DE19962421C1 (de) * 1999-12-22 2001-06-07 Roland Man Druckmasch Verfahren und Vorrichtung zum Kuppeln/Entkuppeln eines Zylinders in einer Druckmaschine
FR2804597B1 (fr) * 2000-02-04 2002-04-26 Soprane Sa Aiguille hyper-elastique
ES2374513T3 (es) * 2002-07-17 2012-02-17 Tyco Healthcare Group Lp Aguja de sutura quirúrgica.
EP1549228A4 (de) * 2002-07-17 2010-04-07 Tyco Healthcare Chirurgische se-nähnadel
AU2003256541A1 (en) * 2002-07-17 2004-02-02 Tyco Healthcare Group Lp Union stress needle
EP1545329B1 (de) * 2002-10-04 2012-07-11 Tyco Healthcare Group LP Spitze nadel
US7185524B2 (en) * 2003-08-14 2007-03-06 Tyco Healthcare Group Lp Grindless surgical needle manufacture
US6926720B2 (en) * 2003-10-15 2005-08-09 Hand Innovations, Llc Jig assembly for implantation of a fracture fixation device
US7353683B2 (en) * 2004-02-20 2008-04-08 Tyco Healthcare Group Lp Surgical needle manufacturing process
US8292920B2 (en) * 2005-11-10 2012-10-23 Tyco Healthcare Group Lp Sickle needle and method
US7415858B2 (en) 2006-02-21 2008-08-26 Tyco Healthcare Group Lp Grindless surgical needle manufacture
CN102014765B (zh) * 2008-04-30 2021-01-01 马尼株式会社 医疗用缝合针
FR2938421B1 (fr) * 2008-11-19 2011-08-05 Fournitures Hospitalieres Ind Aiguille de suture pour la reparation chirurgicale d'un tendon rompu
US9238093B2 (en) * 2011-11-21 2016-01-19 Medtronic, Inc Surface improvement on electric discharge machined titanium alloy miniature parts for implantable medical device
WO2014143901A1 (en) * 2013-03-15 2014-09-18 The Cleveland Clinic Foundation Devices and methods for tissue graft delivery
US10342650B2 (en) 2013-09-27 2019-07-09 Covidien Lp Skirted hernia repair device
US10260135B2 (en) * 2015-03-11 2019-04-16 Soprane Hyperelastic needles
JP6668076B2 (ja) * 2016-01-06 2020-03-18 マニー株式会社 医療用縫合針
JP6319728B2 (ja) * 2016-07-14 2018-05-09 株式会社Ｓｍｒ 縫合針の検査方法、及び縫合針検査装置
TWI631925B (zh) * 2017-03-31 2018-08-11 國立臺灣科技大學 醫療用針具及維持針具銳利度之方法
US10960147B2 (en) 2018-04-20 2021-03-30 Flextronics Ap, Llc Flex needle
USD936828S1 (en) * 2019-02-22 2021-11-23 Ethicon, Inc. Bendable suture needle
USD895114S1 (en) * 2019-02-22 2020-09-01 Ethicon, Inc. Bent suture needle
USD937417S1 (en) * 2019-02-22 2021-11-30 Ethicon, Inc. Foldable suture needle
USD920512S1 (en) * 2019-02-22 2021-05-25 Ethicon, Inc. Folded suture needle
USD938031S1 (en) * 2019-07-14 2021-12-07 Telma Micro Needles Pvt. Ltd. Undrilled needle
CN116352252A (zh) 2019-11-08 2023-06-30 麻省理工学院 激光辅助材料相变和喷出微加工工艺

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DE3434218A1 (de) * 1983-09-19 1985-04-04 Ethicon, Inc., Somerville, N.J. Sterile chirurgische nadel und verfahren zu ihrer herstellung
DE9014387U1 (de) * 1990-10-17 1990-12-20 Singer Spezialnadelfabrik GmbH, 5102 Würselen Chirurgische Nadel
EP0424152A1 (de) * 1989-10-19 1991-04-24 Ethicon, Inc. Konfiguration einer chirurgischen Nadel mit einem sternförmigen Querschnitt
WO1992005809A2 (en) * 1990-09-27 1992-04-16 Allergan, Inc. Single stitch suture needle and method
EP0494648A2 (de) * 1991-01-07 1992-07-15 United States Surgical Corporation Silikonisierte chirurgische Nadel

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JPH03289951A (ja) * 1990-04-05 1991-12-19 Matsutani Seisakusho Co Ltd 刃付縫合針
US5263974A (en) * 1991-01-09 1993-11-23 Matsutani Seisakusho Co., Ltd. Suture needle and method of and apparatus for grinding material for suture needle

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3434218A1 (de) * 1983-09-19 1985-04-04 Ethicon, Inc., Somerville, N.J. Sterile chirurgische nadel und verfahren zu ihrer herstellung
EP0424152A1 (de) * 1989-10-19 1991-04-24 Ethicon, Inc. Konfiguration einer chirurgischen Nadel mit einem sternförmigen Querschnitt
WO1992005809A2 (en) * 1990-09-27 1992-04-16 Allergan, Inc. Single stitch suture needle and method
DE9014387U1 (de) * 1990-10-17 1990-12-20 Singer Spezialnadelfabrik GmbH, 5102 Würselen Chirurgische Nadel
EP0494648A2 (de) * 1991-01-07 1992-07-15 United States Surgical Corporation Silikonisierte chirurgische Nadel

Also Published As

Publication number Publication date
JP2004275789A (ja) 2004-10-07
EP0633000A2 (de) 1995-01-11
EP0633000B1 (de) 1998-05-13
JPH07400A (ja) 1995-01-06
AU3320497A (en) 1997-10-23
DE69426785D1 (de) 2001-04-05
AU677822B2 (en) 1997-05-08
KR940023444A (ko) 1994-11-17
EP0813841B1 (de) 2001-02-28
CA2122418C (en) 1999-09-21
AU6180194A (en) 1994-11-03
DE69410170T2 (de) 1998-10-08
AU707402B2 (en) 1999-07-08
DK0633000T3 (da) 1998-10-07
DE69426785T2 (de) 2001-08-09
ZA942974B (en) 1995-01-18
TW278028B (de) 1996-06-11
DE69410170D1 (de) 1998-06-18
ES2156325T3 (es) 2001-06-16
US5330441A (en) 1994-07-19
ATE165963T1 (de) 1998-05-15
ATE199306T1 (de) 2001-03-15
CA2122418A1 (en) 1994-10-31
EP0813841A3 (de) 1998-01-07
EP0633000A3 (de) 1995-03-08

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